Laboratory Studies

Laboratory testing

The creatine kinase (CK) level is typically normal in SMA type I and normal or slightly elevated in the other types.

CSF findings are normal.

Genetic testing

Both prenatal and postnatal tests are now commercially available.

Homozygous SMN1 gene deletion is 95% sensitive and nearly 100% specific for the diagnosis of SMA. In patients with suspected disease and no gene deletion, SMN1 copy testing with sequencing of coding regions of SMN1 copy (if present) is suggested.
[38] Molecular testing for homozygous deletion or mutation of the SMN1 gene allows efficient and specific diagnosis.
[39]

The 1992 ISMAC found that the accuracy of prenatal prediction by means of chorionic villi sampling and amniocentesis was 88-99%.

Caution should be exercised when prenatal prediction is done in the presence of atypical features (see SMA variants in Physical) because these clinical variations may represent other pathogenic processes.

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Other Tests

Electrophysiologic studies are useful in differentiating the spinal muscular atrophies from other neurogenic and myopathic diseases.
[41, 42] With the exception of Kennedy and Davidenkow syndromes, sensory nerve conduction is normal in spinal muscular atrophy.

Compound motor action potentials (CMAPs) are low normal or reduced, depending on the severity of disease. In chronically weak muscles, CMAPs may be in the near-normal because of reinnervation and collateral sprouting. Motor velocities are normal. Modest slowing of motor conduction, when present, may accompany severe motor axon loss because of the loss of the fastest-conducting motor fibers.

In affected muscles, needle-electrode examination reveals widespread broad and polyphasic motor unit potentials (MUPs) firing in a reduced or rapid neurogenic recruitment pattern. Superimposed low-amplitude, short-duration, and polyphasic MUPs may be present. These configuration changes may resemble myopathic MUPs, but in the case of spinal muscular atrophy are instead due to early MUP reinnervation. Fibrillation potentials may be seen in limb and paraspinal muscles and are most striking in early or progressive spinal muscular atrophy. In late-juvenile and adult-onset forms, active motor axon loss is sparse. Fasciculation potentials are uncommon, but spontaneously firing motor unit action potentials (MUAPs) at 5-15 Hz have been described as a unique feature of SMA I and II.

Mild pseudomyotonic discharges have been observed in patients older than 6 years. However, these discharges are not specific for etiology and may be seen in chronic neurogenic disorders.

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Procedures

Muscle biopsy may necessary to differentiate spinal muscular atrophies from other neuromuscular disorders if genetic analysis is unrevealing. Muscle selection should be centered on clinically affected muscles but not to such a degree that degeneration renders the tissue unrecognizable.

Adequate results can be obtained with open or needle biopsy as long as the physician has adequate experience in the procedure and in processing of the tissue.

Electron microscopy can be used to evaluate for storage diseases.

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Histologic Findings

Histologic findings depend on the stage and progression of disease. Initial changes include atrophy of muscle fibers with compensatory hypertrophy. This results in groups of large and small fibers (fiber-type grouping).

During the first 6-8 weeks of life, differentiating congenital fiber type disproportion and SMA may be difficult. In the chronic forms of SMA, secondary myopathic changes may be seen in addition to type grouping and may histologically resemble the muscular dystrophies.
[43, 44]

Classic histologic findings include the following:

Degeneration and loss of spinal motor neurons with a neurogenic pattern of muscle morphology

Occasional neuronal chromatolysis with loss of myelinated axons in both anterior and posterior roots

A disproportionate loss of myelin in the thoracic and lumbar segments (especially in the corticospinal tracts) with relative sparing of the cervical cord

Motor neurons in the brainstem, notably in the hypoglossal nucleus. (Reactive gliosis and secondary degeneration in roots and nerves are seen. However, these findings are not necessarily pathognomic for the SMAs.)